1. 1. Field of the Invention
The present invention relates to construction of chimeric proteins useful in a potential AIDS vaccine, for development of diagnostic reagents and a process for production thereof. More particularly, the present invention relates to gag chimeric proteins of HIV expressed in recombinant baculovirus infected insect cells, and a process for production thereof. 2. Description of the Prior Art
Types 1 and 2 of the human immunodeficiency viruses (HIV) are recognized as the etiologic agents for acquired immunodeficiency syndrome (AIDS). A vaccine against those viruses would be an ideal way to prevent the development of AIDS from infection with HIV. There has been much research focused on molecular biological analyses of structures and functions of HIV. The main virion structural proteins of HIV are derived from the three structural genes known as gag, pol, env. The genome of many different isolates of HIVs have been completely sequenced and amino acids sequences have been deduced from the cloned proviral DNA sequences. The envelope gene of HIV codes for a glycoprotein precursor with a molecular weight 160,000 (gp160). The precursor gp160 in virus infected cells is processed (or cleaved) to produce envelope glycoprotein gp120 and gp41. The envelope glycoprotein gp120 of HIV has been the major target for developing a candidate vaccine against AIDS. gp120 recognizes the cellular receptor (CD4) on helper T lymphocytes and carries the V3 loop domain that induces neutralizing antibodies (Science 234, 1392-1395, 1986; Proc. Natl. Acad. Science, USA 83, 7023-7027).
The V3 loop represents the third hypervariable region of HIV-1 gp120 (amino acid residues 308-331) which contains not only a major immunodominant neutralizing epitope but also the epitopes for antigen-dependent cellular cytotoxicity (ADCC) and cytotoxic T-lymphocyte (CTL) recognition. Although the majority of the amino acids in the V3 loop are variable among different strains of HIV, a G-P-G-R motif at the tip of the loop is conserved (Science 249, 932-935, 1990).
Recently, Huang et al. and Bjorling et al. demonstrated that the principal neutralization domain of the envelope glycoprotein of HIV-2 is also located in the region corresponding to the hypervariable motif in the V3 loop of HIV-1 gp120. The CD4-binding region, which is located within the C-terminal third of HIV-1 gp120 (amino acid residues 397-439) plays an essential role in infectivity of HIV. This region also seems to be weakly immunogenic because it forms a pocket which is not accessible to the immune system. Thus high-titre neutralizing antibody against this region is not presently available.